Diseases involving retinal vasculature are one of the leading causes of blindness worldwide. Many of these diseases are both progressive and treatable. Thus, their early detection is highly desirable. Diagnoses are often made on the basis of the many structural changes which may occur in the retina as a consequence of problems with retinal blood flow. These problems include neovascularization (the growth of new blood vessels in an attempt to compensate for a reduction in flow through pre-existing vessels), “cotton-wool” patches (regions in which nerve fiber axoplasmic transport has failed), the degeneration of cells of the eye, (e.g., retinal nerve fibers), and/or other metabolic or biochemical abnormalities. Once observed, these and other phenomena may be used to diagnose retinal vascular disease, and treatment may be initiated to inhibit further degeneration. It is desirable to detect such problems early, if possible, before irreversible damage has occurred.
US Patent Application Publication 2006/0147897 to Grinvald et al., which is incorporated herein by reference, describes a method and system for detecting abnormalities in the properties of the walls of a subject's blood vessels by observing the characteristics of blood flow in vessels which are optically accessible, such as the retinal vasculature. A time sequenced series of images is taken, and the images are processed to eliminate the background and render erythrocyte motion visible. Information about the state of the inner wall of the blood vessel which has been imaged is obtained from the characteristics of this blood flow. This information is described as being capable of being extrapolated to provide information about the state of the blood vessels elsewhere in the subject. In addition, a system and method are described for detecting arteriosclerotic plaque on the walls of blood vessels by labeling the plaque with a molecular label having desired optical or radioactive properties, and directly imaging the plaque either in an optically accessible blood vessel, or by imaging radioactive label in the plaque in a blood vessel anywhere in the body.
US Patent Application Publication 2006/0131284 to Grinvald et al., which is incorporated herein by reference, describes a method and system for determining and mapping the quantity of chromophores having a distinct spectrum attached to moving objects in a spectrally rich environment that may include multiple chromophores attached to stationary objects. An area of interest is imaged at different times and different wavelengths, and the spectral properties of the one or more chromophores attached to the moving objects are separated from the stationary spectral properties of the background, followed by spectral analysis of the moving objects to determine their quantity. Application to the retinal vasculature is illustrated, showing the imaging, analyzing and quantifying the oxygen saturation of retinal blood, resolved for the different vascular compartments: capillaries, arterioles, venules, arteries, and veins. Changes in the structure of the vascular environment are also determined (whether growth of new vessels or the elimination of existing ones), by the generation of path maps based on analysis of differential images taken at a single wavelength of the moving components in the blood flow.
U.S. Pat. No. 6,588,901 to Grinvald et al., which is incorporated herein by reference, describes a system for directly imaging and analyzing the movement of individual erythrocytes in blood vessels, the system comprising imaging means for acquiring, within a predetermined time interval from each other, at least one pair of images of at least one same erythrocyte for producing at least two frames, each image representing an analog or digital image of the location of the erythrocyte in each of the frames at a predetermined time; image acquisition means for collecting and storing analog or digital images in machine-readable form, and a computer for controlling the operation of the imaging means and the image acquisition means, for processing the at least two frames, and for analyzing the movement of the erythrocyte in the blood vessels. A method for directly imaging and analyzing the movement of individual erythrocytes in blood vessels is also provided.
U.S. Pat. No. 6,478,424 to Grinvald et al., which is incorporated herein by reference, describes a system for imaging reflectance changes, intrinsic or extrinsic fluorescence changes of a retina due to retinal function, including an imaging illuminator for illumination of the retina; a retina-stimulating illuminator for inducing a functional response; an imaging device receiving light from the retina via retinal imaging optics; image acquisition means for digitizing and storing images received from the imaging device, and a computer for controlling the operation of the system and for processing the stored images to reveal a differential functional signal corresponding to the retina's function.
The following patents and patent applications may be of interest:
PCT Publication WO 06/121,984 to Nelson et al.
U.S. Pat. No. 5,463,426 to Grinvald
PCT Publication Wo 04/049899 to Grinvald et al.
PCT Publication WO 03/083434 to Grinvald et al.
PCT Publication WO 99/063882 to Grinvald et al.
PCT Publication Wo 00/006015 to Grinvald et al.
U.S. Pat. No. 6,351,663 to Flower et al.
U.S. Pat. No. 5,279,298 to Flower
US Patent Application Publication 2002/0016533 to Marchitto et al.
U.S. Pat. No. 5,784,162 to Cabib et al.
U.S. Pat. No. 5,983,120 to Groner et al.
U.S. Pat. No. 6,902,935 to Kaufman
US Patent Application Publication 2002/0111545 to Lindberg
U.S. Pat. No. 6,104,939 to Groner
The following articles may be of interest:
“Retinal microvascular abnormalities and incident stroke: the Atherosclerosis Risk in Communities Study,” by Wong, Lancet 2001: 358:1134-40
“Automatic Extraction and Measurement of Leukocyte Motion in Microvessels Using Spatiotemporal Image Analysis,” by Sato, IEEE Transactions on Biomedical Engineering, Vol. 44, No. 4, April 1997
“Visual stimulus induced changes in human near-infrared fundus reflectance,” by Abramoff, Invest Opthalmol Vis Sci. 2006 February; 47(2): 715-721